This invention relates to an improved package for cryogenically frozen liquid materials, especially in the preservation of valuable biological liquids such as human blood, bone marrow or components thereof. More particularly, the present invention is directed to an improved flexible, slack-fillable, transparent, flat plastic pouch which is readily sterilized and which is capable of being protected against leakage, contamination or other damage by combination with a metal enclosure or retainer comprising parallel metal retaining plates and means to clamp the pouch in a substantially fixed position between said plates. Flexible flat pouches with relatively uniform thin cross sections have been earlier described in such references as Underwood U.S. Pat. No. 3,576,650, and further refinements and improvements in the apparatus and method of flattening and freezing these liquid filled pouches have been disclosed in my U.S. Pat. No. 3,898,023 as well as U.S. Pat. Nos. 3,875,754 and 3,952,536. All of these references stress the importance of maintaining a uniform cross section as the liquid is frozen at cryogenic temperatures so as to permit the carefully controlled rapid freeze and thaw rates needed to prevent damage to the cells or other components of the biological material. It is further noted that this object is more easily achieved by the use of thin, rigid stainless steel liquid containers in place of plastic pouches or bags, but the use of such steel containers has many other disadvantages including venting problems, lack of transparency to inspect the contents and the inherent difficulty of maintaining sterility of the container and its contents. Moreover, the cost of such steel containers is quite high and they cannot be reused.
On the other hand, flat plastic pouches when used as sterile containers for cryogenically frozen liquids continue to cause problems even when properly filled and rapidly frozen into a thin, relatively uniform cross section free of bubbles and protected between a pair of metal plates. Thus, as noted in U.S. Pat. Nos. 3,952,536 and 3,875,754, it is advisable to protect against drop damage by loading the slack filled pouches transversely into restraining plates, i.e. so that the heat seals along opposite edges of the pouch are arranged parallel to the open sides of the restraining plates and at right angles to their closure returns. Moreover, it was found necessary to fold the heat seals over or under the flattened pouch prior to closing the plates and freezing. While this careful assembly helps to prevent pouch rupture when the frozen package is dropped on a concrete floor, the resulting pouch no longer retains a uniform cross section due to necking down of the pouch at the folds and displacement of liquid contents by the folded over parts, especially by the inlet and outlet ports with their tubular inserts.
The use of ridges or dimples which interrupt the flat plate surfaces in these prior patents was recommended to immobilize or lock the pouch in place, especially when frozen, but again such measures reduce the uniformity of the cross section of the slack filled pouch. And due to the slight flexibility of the restraining plates, such measures alone do not effectively prevent movement of the frozen pouch and rupture of a heat sealed edge if dropped on edge or on a corner.
Another problem in the use of prior metal containers or retainers arises in the handling of the package after it has been frozen at a very low temperature, e.g. on the order of about that of liquid nitrogen (-193.degree. C.). Only a very slight rupture or puncture may occur without immediate detection causing a severe disaster when the biological material is later thawed and placed in use. In general, the metal container or retainer must be carefully handled with special tools or by heavily insulated hands, and in either case, the handling becomes relatively difficult and clumsy so as to increase the probability of accidentally dropping the package and rupturing the frozen pouch. Moreover, it is difficult to grasp the container in order to open or close it carefully when inserting or removing the pouch. It is important to maintain the integrity of the entire package during rapid freezing, storage and subsequent use, and prior packages have not substantially reduced the risk of accidental mishandling and the consequential damage to the package and contamination of the biological material.